Role of the CD247 Gene in Celiac Disease Autoimmunity: Genetics vs. Environment

Celiac.com 03/20/2025 - Celiac disease is an autoimmune condition triggered by the ingestion of gluten, affecting individuals with genetic predispositions. Recent research has explored the relationship between genetic factors and environmental influences in the early development of celiac disease autoimmunity. A large study, conducted through the TEDDY birth cohort, investigated how season of birth, viral infections, and genetic variations in the CD247 gene contribute to the risk of developing celiac disease autoimmunity. The findings shed new light on how these factors interact and may help in identifying at-risk individuals earlier.

Materials and Methods

The study was conducted as part of The Environmental Determinants of Diabetes in the Young (TEDDY) project, an observational study designed to track environmental triggers of autoimmune diseases such as type 1 diabetes and celiac disease. TEDDY followed children from birth to the age of 15 years, spanning three research centers in both the United States and Europe.

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Participants were selected based on genetic screening for specific high-risk HLA haplotypes. The initial screening involved 424,788 infants, out of which 21,583 carried the relevant genetic markers. From this group, 8,676 families agreed to participate, and 6,523 children were ultimately included in long-term monitoring for celiac disease autoimmunity. These children were followed until the age of 10, with 1,262 (19.4%) developing celiac disease autoimmunity. The median age for seropositivity was 3.3 years, with the earliest documented case occurring at just 10 months of age.

Regular follow-ups were conducted quarterly until the children turned four, after which visits were scheduled biannually. Early life health data was gathered through maternal questionnaires administered three months postpartum, while additional information about infections and dietary habits was collected from caregiver-maintained diaries. These records included details on the nature, onset, and medical diagnosis of illnesses, as well as the timing of gluten introduction.

Season of Birth and Autoimmunity Risk

One of the significant findings of the study is that the risk of developing celiac disease autoimmunity varies depending on the season in which a child is born. Specifically, children born between March and August were found to be at a higher risk compared to those born in other months. This suggests that environmental exposures during pregnancy or early infancy may influence immune system development in ways that predispose certain children to autoimmunity.

The Role of the CD247 Gene

The study identified a specific genetic factor that interacts with seasonal birth effects. The CD247 gene, which plays a crucial role in immune system signaling, was found to influence the risk of developing celiac disease autoimmunity. Children who had a particular genetic variation (AA genotype of the rs864537 variant) in the CD247 gene and were born in the spring or summer months were at an increased risk. This suggests that the genetic makeup of the immune system interacts with seasonal environmental exposures, influencing disease development.

Early-Life Infections and Immune Response

Another important finding was the relationship between febrile infections during infancy and the development of celiac disease autoimmunity. Children with the AA genotype in the CD247 gene who experienced infections between the ages of three to six months had an elevated risk. This suggests that immune responses to infections during critical periods of immune development may contribute to the onset of autoimmunity.

Potential Mechanisms Behind the Findings

Researchers suggest that variations in CD247 expression levels may affect immune function from an early age. The study found that children with the high-risk genotype had lower expression of the CD247 gene, which could impact T-cell responses. Since the immune system plays a crucial role in distinguishing harmful substances from harmless ones, changes in immune signaling pathways could contribute to a loss of tolerance to gluten, leading to celiac disease.

Interaction Between Diet and Immune Development

The study also examined how diet influences autoimmunity risk. It was found that the increased risk associated with season of birth and genetics was only present in children who were introduced to gluten before seven months of age. This suggests that early exposure to gluten, in combination with genetic and environmental factors, may play a role in triggering celiac disease autoimmunity. However, breastfeeding did not appear to have a strong protective effect in this particular study.

Implications for People with Celiac Disease

These findings highlight the complex interplay between genetic predisposition and environmental factors in the development of celiac disease. The study provides valuable insights that could help refine risk models and guide future research into prevention strategies. Understanding the role of CD247 in immune function may also lead to new approaches for early detection and potential interventions to reduce the risk of celiac disease autoimmunity.

Conclusion

This study underscores the importance of considering both genetic and environmental factors in understanding autoimmune diseases like celiac disease. The discovery that season of birth, infections, and genetic variations interact to influence disease risk provides new directions for research and potential clinical applications. In the future, screening for genetic risk factors combined with environmental monitoring may help identify children at higher risk, leading to earlier interventions and improved management of celiac disease.

Read more at: nature.com